Identifier

etd-04152013-162204

Degree

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

Document Type

Dissertation

Abstract

Spotted fever group (SFG) Rickettsia are obligate intracellular bacteria that are carried by ticks. One such tick, Dermacentor variabilis is a vector for the etiologic agent of Rocky Mountain spotted fever, R. rickettsii. These ticks also carry a non-pathogenic R. montanensis, the agent used in this study. Interestingly, field data collected from infected D. variabilis throughout the United States revealed that the majority of Rickettsia in ticks are non-pathogenic species such as R. montanensis. Although ticks serve as both vector and reservoir hosts for SFG Rickettsia, many questions regarding tick-Rickettsia interaction remain unresolved. Therefore, the overall goal of this research was to study the relationship between ticks and Rickettsia, specifically examining the molecular mechanisms of rickettsial infection of tick host. As SFG Rickettsia can move between vertebrate and invertebrate hosts, the hypothesis is that conserved mechanisms are utilized for invasion of both types of host cell. Biochemical inhibition assays revealed that the tick molecules, PI 3-kinase, protein tyrosine kinases, Src, FAK, Rho GTPase Rac1, N-WASP, Arp2/3 complex, actin, and V-ATPase are important for R. montanensis invasion. Further studies were executed to molecularly and functionally characterize the tick molecules, Arp2/3 complex and V-ATPase, which are central to rickettsial internalization. Full length cDNA of Arp2/3 complex subunits and V-ATPase from D. variabilis were isolated. Transcriptional profiles of Arp2/3 complex subunits and V-ATPase showed greater expression of the mRNA in tick ovaries compared to midgut and salivary glands. In addition, to gain insight into rickettsial invasion in nature, Arp2/3 complex inhibition assays were performed in tick tissues. The results demonstrated the involvement of Arp2/3 complex in rickettsial entry into midgut, ovary, and salivary glands. The tick molecules identified in this study may provide novel points of intervention in the transmission of tick-borne rickettsial diseases.

Date

2013

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Macaluso, Kevin R.

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